Ob.Gyn. News

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.¹ These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.²

In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally. 
 

Mechanism of coagulopathy

COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.³ Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.^2,5,6

Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.⁴

It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.⁷ COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.⁸

Clinical and laboratory abnormalities

A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.³

Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.^9,10 In a retrospective analysis⁹ by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.⁹ In addition, elevated ^d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.

Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.¹¹

COVID-19 coagulopathy management

In a retrospective study⁹ of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.¹²

Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.¹³

Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.¹¹ Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 10⁹/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.¹² This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.^14,15

Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x10⁹/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.¹¹ Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.¹⁶

COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x10⁹/L or if the fibrinogen is less than 1.0 g/L.¹⁶

Conclusion

Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.

Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.

References

1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.

2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.

3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.

4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575. 

5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.

6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362. 

7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319. 

8.  Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.

9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847. 

10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.

11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810. 

12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817. 

13.  Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.

14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.

15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.

16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.¹ These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.²

In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally. 
 

Mechanism of coagulopathy

COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.³ Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.^2,5,6

Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.⁴

It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.⁷ COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.⁸

Clinical and laboratory abnormalities

A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.³

Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.^9,10 In a retrospective analysis⁹ by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.⁹ In addition, elevated ^d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.

Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.¹¹

COVID-19 coagulopathy management

In a retrospective study⁹ of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.¹²

Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.¹³

Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.¹¹ Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 10⁹/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.¹² This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.^14,15

Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x10⁹/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.¹¹ Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.¹⁶

COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x10⁹/L or if the fibrinogen is less than 1.0 g/L.¹⁶

Conclusion

Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.

Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.

References

1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.

2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.

3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.

4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575. 

5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.

6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362. 

7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319. 

8.  Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.

9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847. 

10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.

11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810. 

12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817. 

13.  Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.

14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.

15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.

16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.¹ These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.²

In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally. 
 

Mechanism of coagulopathy

COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.³ Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.^2,5,6

Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.⁴

It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.⁷ COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.⁸

Clinical and laboratory abnormalities

A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.³

Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.^9,10 In a retrospective analysis⁹ by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.⁹ In addition, elevated ^d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.

Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.¹¹

COVID-19 coagulopathy management

In a retrospective study⁹ of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.¹²

Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.¹³

Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.¹¹ Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 10⁹/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.¹² This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.^14,15

Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x10⁹/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.¹¹ Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.¹⁶

COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x10⁹/L or if the fibrinogen is less than 1.0 g/L.¹⁶

Conclusion

Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.

Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.

References

1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.

2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.

3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.

4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575. 

5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.

6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362. 

7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319. 

8.  Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.

9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847. 

10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.

11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810. 

12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817. 

13.  Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.

14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.

15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.

16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

sworcester@mdedge.com

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

sworcester@mdedge.com

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

sworcester@mdedge.com

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

Differences in COVID-19-related death rates between people of white and Asian ancestry may be partly explained by documented ethnic/racial differences in risk for blood clotting and pulmonary thrombotic events, investigators propose.

“Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focused within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19,” said James O’Donnell, MB, PhD, director of the Irish Centre for Vascular Biology at the Royal College of Surgeons in Ireland.

Dr. O’Donnell and colleagues studied pulmonary effects and outcomes of 83 patients admitted to St. James Hospital in Dublin, and found evidence to suggest that the diffuse, bilateral pulmonary inflammation seen in many patients with severe COVID-19 infections may be caused by a pulmonary-specific vasculopathy they label “pulmonary intravascular coagulopathy” (PIC), an entity distinct from disseminated intravascular coagulopathy (DIC).

“Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID-19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID-19 mortality,” they wrote in a study published online in the British Journal of Haematology.
 

Study flaws harm conclusions

But critical care specialists who agreed to review and comment on the study for MDedge News said that it has significant flaws that affect the ability to interpret the findings and “undermine the conclusions reached by the authors.”

“The underlying premise of the study is that there are racial and ethnic differences in the development of venous thromboembolism that may explain the racial and ethnic differences in outcomes from COVID-19,” J. Daryl Thornton, MD, MPH, a fellow of the American Thoracic Society and associate professor of pulmonary, critical care, and sleep medicine at Case Western Reserve University, Cleveland, said in an interview. “This is an interesting hypothesis and one that could be easily tested in a well-designed study with sufficient representation from the relevant racial and ethnic groups. However, this study is neither well designed nor does it have sufficient racial and ethnic representation.”

Elliott R. Haut, MD, PhD, associate professor of surgery, anesthesiology and critical care medicine at Johns Hopkins Medicine, Baltimore, said in an interview that the study is “mediocre” and has the feel of a paper rushed to press.

“It talks about their theory that race, ethnicity, have an effect on venous thromboembolism, and that’s a pretty well-known fact. No one’s a hundred percent sure why that is, but certainly there are tons and tons of papers that show that there are groups that are at higher risk than others,” he said. “Their idea that this is caused by this pulmonary inflammation, that is totally a guess; there is no data in this paper to support that.”

Dr. Thornton and Dr. Haut both noted that the authors don’t define how race and ethnicity were determined and whether patients were asked to provide it, and although they mention the racial/ethnic breakdown once, subsequent references are to entire cohort are as “Caucasian.”

They also called into question the value of comparing laboratory data across continents in centers with different testing methods and parameters, especially in a time when the clinical picture changes so rapidly.
 

Coagulation differences

Dr. O’Donnell and colleagues noted that most studies of COVID-19-associated coagulopathy published to date have been with Chinese patients.

“This is important because race and ethnicity have major effects upon thrombotic risk. In particular, epidemiological studies have shown that the incidence of venous thromboembolism (VTE) is approximately three to fourfold lower in Chinese compared to Caucasian individuals. Conversely, VTE risk is significantly higher in African-Americans compared to Caucasians,” they wrote.

Because of the lower risk of VTE in the Chinese population, thromboprophylaxis with low-molecular-weight heparin (LMWH) or other agents is less frequently used in Chinese hospitals than in hospitals with predominantly non-Asian patients, they noted.

To see whether the were differences in coagulopathy between Chinese and white patients, the researchers enrolled 55 men and 28 women, median age 64, who were admitted to St. James Hospital with COVID-19 infections from March 13 through April 10, 2020. The cohort included 67 patients of white background, 10 of Asian ancestry, 5 of African ethnicity, and 1 of Latino/Hispanic ancestry.

Of the 83 patients, 67 had comorbidities at admission. At the time of the report, 50 patients had fully recovered and were discharged, 20 remained in the hospital, and 13 had died. In all, 50 patients were discharged without needing ICU care, 23 were admitted to the ICU, and 10 required ICU but were deemed “clinically unsuitable” for ICU admission.

Although the patients had normal prothrombin time (PT) and normal activated partial thromboplastin time (APTT), plasma d-dimer levels were significantly elevated and were above the range of normal in two-thirds of patients on admission.

Despite the increased d-dimer levels, however, there was no evidence of DIC as defined by the International Society of Thrombosis and Hemostasis Scientific and Standardization committee (ISTH SSC) guidelines. Platelet counts were in the normal range in 83.1% of patients, and only five had counts less than 100 x 109/L at admission. Fibrinogen levels were also elevated, as were C-reactive protein levels, both likely indicating an acute phase response.

“Thus, despite the fact that thrombotic risk is much higher in Caucasian patients and the significant elevated levels of d-dimers observed, overt DIC as defined according to the ISTH SSC DIC score was present in none of our COVID-19 patients at time of admission. Nevertheless, our data confirm that severe COVID-19 infection is associated with a significant coagulopathy in Caucasian patients that appears to be similar in magnitude to that previously reported in the original Chinese cohorts,” they wrote.

When they compared patients who required ICU admission for ventilator support and those who died with patients who were discharged without needing ICU support, they found that survivors were younger (median age 60.2 vs. 75.2 years), and that more critically ill patients were more likely to have comorbidities.

They also found that patients with abnormal coagulation parameters on admission were significantly more likely to have poor prognosis (P = .018), and that patients in the adverse outcomes group had significantly higher fibrinogen and CRP levels (P = .045 and .0005, respectively).

There was no significant difference in PT between the prognosis groups at admission, but by day 4 and beyond PT was a median of 13.1 vs. 12.5 seconds in the favorable outcomes groups (P = .007), and patients with poor prognosis continued to have significantly higher d-dimer levels. (P = .003)

“Cumulatively, these data support the hypothesis that COVID-19–associated coagulopathy probably contributes to the underlying pulmonary pathogenesis,” the researchers wrote.

They noted that the angiotensin converting enzyme 2 (ACE-2) receptor that COVID-19 uses to enter cells is expressed on both type II pneumocytes and vascular endothelial cells within the lung, suggesting that the coagulopathy may be related to direct pulmonary endothelial cell infection , activation, and/or damage, and to the documented cytokine storm that can affect thrombin generation and fibrin deposition within the lungs.

“In the context of this lung-centric vasculopathy, we hypothesize that the refractory acute respiratory distress syndrome phenotype observed in severe COVID-19 is due to concurrent ‘double-hit’ pathologies targeting both ventilation (V) and perfusion (Q) within the lungs where alveoli and pulmonary microvasculature exist in close anatomical juxtaposition,” they wrote.

The investigators noted that larger randomized trials will be needed to determine whether more aggressive anti-coagulation and/or targeted anti-inflammatory therapies could effectively treated PIC in patients with severe COVID-19.

The study was supported by the Wellcome Trust and the Health Research Board Health Service and the Research and Development Division, Northern Ireland. Dr. O’Donnell disclosed speakers bureau activities, advisory board participation, and research grants from multiple companies. The other doctors had no relevant conflicts of interest to disclose.

SOURCE: Fogarty H et al. Br J Haematol. 2020 Apr 24. doi: 10.1111/bjh.16749.

Differences in COVID-19-related death rates between people of white and Asian ancestry may be partly explained by documented ethnic/racial differences in risk for blood clotting and pulmonary thrombotic events, investigators propose.

“Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focused within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19,” said James O’Donnell, MB, PhD, director of the Irish Centre for Vascular Biology at the Royal College of Surgeons in Ireland.

Dr. O’Donnell and colleagues studied pulmonary effects and outcomes of 83 patients admitted to St. James Hospital in Dublin, and found evidence to suggest that the diffuse, bilateral pulmonary inflammation seen in many patients with severe COVID-19 infections may be caused by a pulmonary-specific vasculopathy they label “pulmonary intravascular coagulopathy” (PIC), an entity distinct from disseminated intravascular coagulopathy (DIC).

“Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID-19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID-19 mortality,” they wrote in a study published online in the British Journal of Haematology.
 

Study flaws harm conclusions

But critical care specialists who agreed to review and comment on the study for MDedge News said that it has significant flaws that affect the ability to interpret the findings and “undermine the conclusions reached by the authors.”

“The underlying premise of the study is that there are racial and ethnic differences in the development of venous thromboembolism that may explain the racial and ethnic differences in outcomes from COVID-19,” J. Daryl Thornton, MD, MPH, a fellow of the American Thoracic Society and associate professor of pulmonary, critical care, and sleep medicine at Case Western Reserve University, Cleveland, said in an interview. “This is an interesting hypothesis and one that could be easily tested in a well-designed study with sufficient representation from the relevant racial and ethnic groups. However, this study is neither well designed nor does it have sufficient racial and ethnic representation.”

Elliott R. Haut, MD, PhD, associate professor of surgery, anesthesiology and critical care medicine at Johns Hopkins Medicine, Baltimore, said in an interview that the study is “mediocre” and has the feel of a paper rushed to press.

“It talks about their theory that race, ethnicity, have an effect on venous thromboembolism, and that’s a pretty well-known fact. No one’s a hundred percent sure why that is, but certainly there are tons and tons of papers that show that there are groups that are at higher risk than others,” he said. “Their idea that this is caused by this pulmonary inflammation, that is totally a guess; there is no data in this paper to support that.”

Dr. Thornton and Dr. Haut both noted that the authors don’t define how race and ethnicity were determined and whether patients were asked to provide it, and although they mention the racial/ethnic breakdown once, subsequent references are to entire cohort are as “Caucasian.”

They also called into question the value of comparing laboratory data across continents in centers with different testing methods and parameters, especially in a time when the clinical picture changes so rapidly.
 

Coagulation differences

Dr. O’Donnell and colleagues noted that most studies of COVID-19-associated coagulopathy published to date have been with Chinese patients.

“This is important because race and ethnicity have major effects upon thrombotic risk. In particular, epidemiological studies have shown that the incidence of venous thromboembolism (VTE) is approximately three to fourfold lower in Chinese compared to Caucasian individuals. Conversely, VTE risk is significantly higher in African-Americans compared to Caucasians,” they wrote.

Because of the lower risk of VTE in the Chinese population, thromboprophylaxis with low-molecular-weight heparin (LMWH) or other agents is less frequently used in Chinese hospitals than in hospitals with predominantly non-Asian patients, they noted.

To see whether the were differences in coagulopathy between Chinese and white patients, the researchers enrolled 55 men and 28 women, median age 64, who were admitted to St. James Hospital with COVID-19 infections from March 13 through April 10, 2020. The cohort included 67 patients of white background, 10 of Asian ancestry, 5 of African ethnicity, and 1 of Latino/Hispanic ancestry.

Of the 83 patients, 67 had comorbidities at admission. At the time of the report, 50 patients had fully recovered and were discharged, 20 remained in the hospital, and 13 had died. In all, 50 patients were discharged without needing ICU care, 23 were admitted to the ICU, and 10 required ICU but were deemed “clinically unsuitable” for ICU admission.

Although the patients had normal prothrombin time (PT) and normal activated partial thromboplastin time (APTT), plasma d-dimer levels were significantly elevated and were above the range of normal in two-thirds of patients on admission.

Despite the increased d-dimer levels, however, there was no evidence of DIC as defined by the International Society of Thrombosis and Hemostasis Scientific and Standardization committee (ISTH SSC) guidelines. Platelet counts were in the normal range in 83.1% of patients, and only five had counts less than 100 x 109/L at admission. Fibrinogen levels were also elevated, as were C-reactive protein levels, both likely indicating an acute phase response.

“Thus, despite the fact that thrombotic risk is much higher in Caucasian patients and the significant elevated levels of d-dimers observed, overt DIC as defined according to the ISTH SSC DIC score was present in none of our COVID-19 patients at time of admission. Nevertheless, our data confirm that severe COVID-19 infection is associated with a significant coagulopathy in Caucasian patients that appears to be similar in magnitude to that previously reported in the original Chinese cohorts,” they wrote.

When they compared patients who required ICU admission for ventilator support and those who died with patients who were discharged without needing ICU support, they found that survivors were younger (median age 60.2 vs. 75.2 years), and that more critically ill patients were more likely to have comorbidities.

They also found that patients with abnormal coagulation parameters on admission were significantly more likely to have poor prognosis (P = .018), and that patients in the adverse outcomes group had significantly higher fibrinogen and CRP levels (P = .045 and .0005, respectively).

There was no significant difference in PT between the prognosis groups at admission, but by day 4 and beyond PT was a median of 13.1 vs. 12.5 seconds in the favorable outcomes groups (P = .007), and patients with poor prognosis continued to have significantly higher d-dimer levels. (P = .003)

“Cumulatively, these data support the hypothesis that COVID-19–associated coagulopathy probably contributes to the underlying pulmonary pathogenesis,” the researchers wrote.

They noted that the angiotensin converting enzyme 2 (ACE-2) receptor that COVID-19 uses to enter cells is expressed on both type II pneumocytes and vascular endothelial cells within the lung, suggesting that the coagulopathy may be related to direct pulmonary endothelial cell infection , activation, and/or damage, and to the documented cytokine storm that can affect thrombin generation and fibrin deposition within the lungs.

“In the context of this lung-centric vasculopathy, we hypothesize that the refractory acute respiratory distress syndrome phenotype observed in severe COVID-19 is due to concurrent ‘double-hit’ pathologies targeting both ventilation (V) and perfusion (Q) within the lungs where alveoli and pulmonary microvasculature exist in close anatomical juxtaposition,” they wrote.

The investigators noted that larger randomized trials will be needed to determine whether more aggressive anti-coagulation and/or targeted anti-inflammatory therapies could effectively treated PIC in patients with severe COVID-19.

The study was supported by the Wellcome Trust and the Health Research Board Health Service and the Research and Development Division, Northern Ireland. Dr. O’Donnell disclosed speakers bureau activities, advisory board participation, and research grants from multiple companies. The other doctors had no relevant conflicts of interest to disclose.

SOURCE: Fogarty H et al. Br J Haematol. 2020 Apr 24. doi: 10.1111/bjh.16749.

Differences in COVID-19-related death rates between people of white and Asian ancestry may be partly explained by documented ethnic/racial differences in risk for blood clotting and pulmonary thrombotic events, investigators propose.

“Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focused within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19,” said James O’Donnell, MB, PhD, director of the Irish Centre for Vascular Biology at the Royal College of Surgeons in Ireland.

Dr. O’Donnell and colleagues studied pulmonary effects and outcomes of 83 patients admitted to St. James Hospital in Dublin, and found evidence to suggest that the diffuse, bilateral pulmonary inflammation seen in many patients with severe COVID-19 infections may be caused by a pulmonary-specific vasculopathy they label “pulmonary intravascular coagulopathy” (PIC), an entity distinct from disseminated intravascular coagulopathy (DIC).

“Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID-19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID-19 mortality,” they wrote in a study published online in the British Journal of Haematology.
 

Study flaws harm conclusions

But critical care specialists who agreed to review and comment on the study for MDedge News said that it has significant flaws that affect the ability to interpret the findings and “undermine the conclusions reached by the authors.”

“The underlying premise of the study is that there are racial and ethnic differences in the development of venous thromboembolism that may explain the racial and ethnic differences in outcomes from COVID-19,” J. Daryl Thornton, MD, MPH, a fellow of the American Thoracic Society and associate professor of pulmonary, critical care, and sleep medicine at Case Western Reserve University, Cleveland, said in an interview. “This is an interesting hypothesis and one that could be easily tested in a well-designed study with sufficient representation from the relevant racial and ethnic groups. However, this study is neither well designed nor does it have sufficient racial and ethnic representation.”

Elliott R. Haut, MD, PhD, associate professor of surgery, anesthesiology and critical care medicine at Johns Hopkins Medicine, Baltimore, said in an interview that the study is “mediocre” and has the feel of a paper rushed to press.

“It talks about their theory that race, ethnicity, have an effect on venous thromboembolism, and that’s a pretty well-known fact. No one’s a hundred percent sure why that is, but certainly there are tons and tons of papers that show that there are groups that are at higher risk than others,” he said. “Their idea that this is caused by this pulmonary inflammation, that is totally a guess; there is no data in this paper to support that.”

Dr. Thornton and Dr. Haut both noted that the authors don’t define how race and ethnicity were determined and whether patients were asked to provide it, and although they mention the racial/ethnic breakdown once, subsequent references are to entire cohort are as “Caucasian.”

They also called into question the value of comparing laboratory data across continents in centers with different testing methods and parameters, especially in a time when the clinical picture changes so rapidly.
 

Coagulation differences

Dr. O’Donnell and colleagues noted that most studies of COVID-19-associated coagulopathy published to date have been with Chinese patients.

“This is important because race and ethnicity have major effects upon thrombotic risk. In particular, epidemiological studies have shown that the incidence of venous thromboembolism (VTE) is approximately three to fourfold lower in Chinese compared to Caucasian individuals. Conversely, VTE risk is significantly higher in African-Americans compared to Caucasians,” they wrote.

Because of the lower risk of VTE in the Chinese population, thromboprophylaxis with low-molecular-weight heparin (LMWH) or other agents is less frequently used in Chinese hospitals than in hospitals with predominantly non-Asian patients, they noted.

To see whether the were differences in coagulopathy between Chinese and white patients, the researchers enrolled 55 men and 28 women, median age 64, who were admitted to St. James Hospital with COVID-19 infections from March 13 through April 10, 2020. The cohort included 67 patients of white background, 10 of Asian ancestry, 5 of African ethnicity, and 1 of Latino/Hispanic ancestry.

Of the 83 patients, 67 had comorbidities at admission. At the time of the report, 50 patients had fully recovered and were discharged, 20 remained in the hospital, and 13 had died. In all, 50 patients were discharged without needing ICU care, 23 were admitted to the ICU, and 10 required ICU but were deemed “clinically unsuitable” for ICU admission.

Although the patients had normal prothrombin time (PT) and normal activated partial thromboplastin time (APTT), plasma d-dimer levels were significantly elevated and were above the range of normal in two-thirds of patients on admission.

Despite the increased d-dimer levels, however, there was no evidence of DIC as defined by the International Society of Thrombosis and Hemostasis Scientific and Standardization committee (ISTH SSC) guidelines. Platelet counts were in the normal range in 83.1% of patients, and only five had counts less than 100 x 109/L at admission. Fibrinogen levels were also elevated, as were C-reactive protein levels, both likely indicating an acute phase response.

“Thus, despite the fact that thrombotic risk is much higher in Caucasian patients and the significant elevated levels of d-dimers observed, overt DIC as defined according to the ISTH SSC DIC score was present in none of our COVID-19 patients at time of admission. Nevertheless, our data confirm that severe COVID-19 infection is associated with a significant coagulopathy in Caucasian patients that appears to be similar in magnitude to that previously reported in the original Chinese cohorts,” they wrote.

When they compared patients who required ICU admission for ventilator support and those who died with patients who were discharged without needing ICU support, they found that survivors were younger (median age 60.2 vs. 75.2 years), and that more critically ill patients were more likely to have comorbidities.

They also found that patients with abnormal coagulation parameters on admission were significantly more likely to have poor prognosis (P = .018), and that patients in the adverse outcomes group had significantly higher fibrinogen and CRP levels (P = .045 and .0005, respectively).

There was no significant difference in PT between the prognosis groups at admission, but by day 4 and beyond PT was a median of 13.1 vs. 12.5 seconds in the favorable outcomes groups (P = .007), and patients with poor prognosis continued to have significantly higher d-dimer levels. (P = .003)

“Cumulatively, these data support the hypothesis that COVID-19–associated coagulopathy probably contributes to the underlying pulmonary pathogenesis,” the researchers wrote.

They noted that the angiotensin converting enzyme 2 (ACE-2) receptor that COVID-19 uses to enter cells is expressed on both type II pneumocytes and vascular endothelial cells within the lung, suggesting that the coagulopathy may be related to direct pulmonary endothelial cell infection , activation, and/or damage, and to the documented cytokine storm that can affect thrombin generation and fibrin deposition within the lungs.

“In the context of this lung-centric vasculopathy, we hypothesize that the refractory acute respiratory distress syndrome phenotype observed in severe COVID-19 is due to concurrent ‘double-hit’ pathologies targeting both ventilation (V) and perfusion (Q) within the lungs where alveoli and pulmonary microvasculature exist in close anatomical juxtaposition,” they wrote.

The investigators noted that larger randomized trials will be needed to determine whether more aggressive anti-coagulation and/or targeted anti-inflammatory therapies could effectively treated PIC in patients with severe COVID-19.

The study was supported by the Wellcome Trust and the Health Research Board Health Service and the Research and Development Division, Northern Ireland. Dr. O’Donnell disclosed speakers bureau activities, advisory board participation, and research grants from multiple companies. The other doctors had no relevant conflicts of interest to disclose.

SOURCE: Fogarty H et al. Br J Haematol. 2020 Apr 24. doi: 10.1111/bjh.16749.

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

A version of this article originally appeared on Medscape.com.

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

A version of this article originally appeared on Medscape.com.

Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring.

Three of the new studies were published in the New England Journal of Medicine on May 1, and one study was published in JAMA Cardiology on May 5.

Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.

Providing commentary, John McMurray, MD, professor of medical cardiology at the University of Glasgow, said: “The overall picture seems to suggest no increase in risk of adverse outcomes in patients taking renin-angiotensin system [RAS] blockers ― but with lots of caveats: These are all observational rather than randomized studies, and there may be residual or unmeasured confounding.”
 

Was it ‘Much ado about nothing’?

Franz Messerli, MD, professor of medicine at the University of Bern (Switzerland), added: “Given this state of the art, I am inclined to consider RAS blockade and COVID-19 – despite all the hype in the news media – as much ado about nothing.”

But both Dr. McMurray and Dr. Messerli said they were intrigued about possible differences in the effects of ACE inhibitors and ARBs that some of the new results suggest.

In one study, a team led by Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center, Boston, analyzed data from 8,910 patients with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%).

In multivariate logistic-regression analysis, age greater than 65 years, coronary artery disease, congestive heart failure, history of cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking were associated with an increased risk for in-hospital death. Female sex was associated with a decreased risk. Neither ACE inhibitors nor ARBs were associated with an increased risk for in-hospital death.

In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio, 0.33), as were statins (OR, 0.35).

The authors, however, stressed that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”

“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they wrote.

A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.

A second study published in the New England Journal of Medicine had a case-control design. The authors, led by Giuseppe Mancia, MD, of the University of Milano-Bicocca (Italy), compared 6,272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.

In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.

“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors concluded.

In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.

In the third study published in the New England Journal of Medicine, a group led by Harmony R. Reynolds, MD, of New York University, analyzed data from the health records of 12,594 patients in the NYU Langone Health system who had been tested for COVID-19. They found 5,894 patients whose test results were positive. Of these patients, 1,002 had severe illness, which was defined as illness requiring admission to the ICU, need for mechanical ventilation, or death.

Using Bayesian analysis and propensity score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and thiazide diuretics) and the likelihood of a positive or negative result on COVID-19 testing, as well as the likelihood of severe illness among patients who tested positive.

Results showed no positive association between any of the analyzed drug classes and either a positive test result or severe illness.

In an accompanying editorial, a group led by John A. Jarcho, MD, of Harvard Medical School, Boston, and deputy editor of the New England Journal of Medicine, wrote: “Taken together, these three studies do not provide evidence to support the hypothesis that ACE inhibitor or ARB use is associated with the risk of SARS-CoV-2 infection, the risk of severe COVID-19 among those infected, or the risk of in-hospital death among those with a positive test.

“Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19. Several other smaller studies from China and the United Kingdom have come to the same conclusion,” the authors of the editorial stated.

In the study published in JAMA Cardiology, a group led by Neil Mehta, MBBS, of the Cleveland Clinic, Ohio, analyzed data on 18,472 patients who had been tested for COVID-19 between March 8 and April 12 in the Cleveland Clinic Health System in Ohio and Florida. Of these patients, 9.4% tested positive.

After overlap propensity score weighting for both ACE inhibitors and ARBs to take into account relevant comorbidities, there was no difference in risk for testing positive among patients taking an ACE inhibitor or an ARB in comparison with those not taking such medication.
 

Are there different effects between ACE inhibitors and ARBs?

A secondary exploratory analysis showed a higher likelihood of hospital admission among patients who tested positive and who were taking either ACE inhibitors (OR, 1.84) or ARBs (OR, 1.61), and there was a higher likelihood of ICU admission among patients who tested positive and who were taking an ACE inhibitor (OR 1.77), but no such difference was observed among those taking ARBs.

Coauthor Ankur Kalra, MD, of the Cleveland Clinic, said in an interview that results of the exploratory analysis fit with the hypothesis that the two drugs classes may have different effects in patients with COVID-19.

“Angiotensin II promotes vasoconstriction, inflammation, and fibrosis in the lungs, and ARBs block the effects of angiotensin II more effectively than ACE inhibitors. In addition, ACE inhibitors (but not ARBs) increase levels of bradykinin, which may be one factor leading to acute respiratory distress syndrome,” he noted.

“However, these results should only be considered exploratory, as there is inherent bias in observational data,” Dr. Kalra stressed.

In an accompanying editorial in JAMA Cardiology, a group led by Laine E. Thomas, PhD, of Duke Clinical Research Institute, Durham, North Carolina, said that the results of this secondary exploratory analysis are limited by a small number of patients and “are likely explained by confounding and should not be inferred as causal.”

The New England Journal of Medicine editorialists reached a similar conclusion regarding the lower mortality in COVID-19 patients who took ACE inhibitors in the study by Dr. Mehra and colleagues. They say this unexpected result “may be due to unmeasured confounding and, in the absence of a randomized trial, should not be regarded as evidence to prescribe these drugs in patients with COVID-19.”

Providing further comment, Dr. McMurray said: “Normally, I would not read too much into the different effects of ACE inhibitors and ARBs suggested in the Cleveland study because of the small numbers (about 28 ACE inhibitor–treated patients admitted to ICU) and the limited information about matching and/or adjustment for potential differences between groups.

“I could also argue that the comparison that would best answer the question about risk related to type of RAS blocker would be the direct comparison of people taking an ACE inhibitor with those taking an ARB (and that doesn’t look very different). The only thing that makes me a little cautious about completely dismissing the possibility of a difference between ACE inhibitor and ARB here is the suggestion of a similar trend in another large study from the VA [Veterans Affairs] system,” he added.

He also noted that speculation about there being mechanisms that involve different effects of the two drug classes on bradykinin and angiotensin II was “plausible but unproven.”

Dr. Messerli added: “Before turning the page, I would like to see an analysis comparing ACE inhibitors and ARBs, since experimentally, their effect on ACE2 (the receptor to which the virus binds) seems to differ. The study of Mehta et al in JAMA Cardiology may be the first clinical hint indicating that ARBs are more protective than ACEIs. However even here, the looming possibility of confounding cannot be excluded.”

Dr. Messerli also pointed to a hypothesis that suggests that direct viral infection of endothelial cells expressing ACE2 receptors may explain worse outcomes in patients with cardiovascular comorbidities, which provides a rationale for therapies to stabilize the endothelium, particularly with anti-inflammatory anticytokine drugs, ACE inhibitors, and statins.

A version of this article originally appeared on Medscape.com.

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

Women with cardiovascular conditions who are planning pregnancy should be assessed and managed by a multidisciplinary team to ensure the best outcomes, according to a statement from the American Heart Association.

©American Heart Association

Cardiovascular disease (CVD) remains the leading cause of pregnancy-related mortality in the United States, and accounted for approximately 17 deaths per 100,000 live births in 2015, wrote Laxmi S. Mehta, MD, of The Ohio State University, Columbus, and colleagues.

Ideally, a woman with CVD at the time of pregnancy should be managed by a multidisciplinary cardio-obstetrics team that can assess cardiovascular risk, obstetric risk, and fetal risk throughout pregnancy, delivery, and up to a year post partum. The team should develop a shared strategy to promote best outcomes, according to the statement. The cardio-obstetrics team may include obstetricians, cardiologists, anesthesiologists, maternal-fetal medicine specialists, geneticists, neurologists, nurses, and pharmacists, according to the statement.

Women with preexisting CVD should receive counseling about maternal and fetal risks before conception, if possible, to involve the women in shared decision-making and to develop strategies for each stage of pregnancy and delivery, Dr. Mehta and associates said. Such counseling should include a review of all medications and assessment of risk factors.

However, some women present already in the early stages of pregnancy even with severe conditions such as pulmonary arterial hypertension, severe ventricular dysfunction, severe left-sided heart obstruction, and significant aortic dilatation with underlying connective tissue disease. Women with these conditions often are counseled to avoid pregnancy, but if they already are pregnant, a high-risk cardio-obstetrics team will need to work together to discover the best strategies going forward to mitigate risk, Dr. Mehta and associates said.

Common CVD conditions that affect pregnancy include hypertensive disorders, notably preeclampsia, defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg in women after 20 weeks of gestation whose blood pressure was normal prior to pregnancy. A management strategy to reduce the risk of pregnancy-related complications from hypertension includes healthy lifestyle behaviors such as exercise, nutrition, and smoking cessation, according to the statement. However, patients with severe hypertension may require intravenous labetalol or hydralazine. The statement gives more information about handling preeclampsia with pulmonary edema, and prevention of eclampsia and treatment of seizures.

It is important to recognize that severe hypertension or superimposed preeclampsia may occur for the first time post partum. Early ambulatory visits in the first 1-2 weeks are sensible. Medications may be needed to keep a systolic blood pressure not higher than 150 mm Hg and a diastolic blood pressure not higher than 100 mm Hg, Dr. Mehta and associates said.

According to the statement, severe hypertriglyceridemia and familial hypercholesterolemia are the two most common conditions in which lipids should be addressed during pregnancy, with consideration of the fetal risks associated with certain medications.

“Statins are contraindicated during pregnancy, and all women who are on any lipid-lowering agents should review with their physician the safety of treatment during pregnancy and whether to discontinue treatment before pregnancy,” according to the statement. A heart-healthy lifestyle can help improve lipid profiles in all pregnant patients, Dr. Mehta and associates said. Patients with extremely high triglycerides above 500 mg/dL are at risk of pancreatitis and “may benefit from pharmacological agents (omega-3 fatty acids with or without fenofibrate or gemfibrozil) during the second trimester,” they noted. Pregnant women with familial hypercholesterolemia might take bile acid sequestrants, or as a last resort, low-density lipoprotein apheresis.

Other conditions calling for a multidisciplinary cardio-obstetric approach include preexisting coronary artery disease, cardiomyopathies, arrhythmias, valvular heart disease, cerebrovascular disease, and deep venous thrombosis, according to the statement, which provides information about the risks, diagnosis, and management.

When it is time for delivery, spontaneous labor and vaginal birth are preferable for most women with heart disease, as cesarean delivery is associated with increased risk of infection, thrombotic complications, and blood loss, according to the statement.

Women with CVD and associated complications will require “specialized long-term cardiovascular follow-up,” Dr. Mehta and associates said. “In women with a high-risk pregnancy, a cardio-obstetrics team is essential to prevent maternal morbidity and mortality during the length of the pregnancy and post partum.”

“The release of this document demonstrates the AHA’s recognition of the importance of CVD in pregnancy-related death and their commitment to education and ensuring best practices in this field,” said Lisa M. Hollier, MD, past president of the American College of Obstetricians and Gynecologists and chief medical officer at Texas Children’s Health Plan, Bellaire.

“I think one of the most important outcomes from the release of this scientific statement from AHA will be increased implementation of cardio-obstetrics teams,” she said in an interview.

“In the United States, cardiovascular disease and cardiomyopathy together are now the leading cause of death in pregnancy and the postpartum period, and constitute 26.5% of pregnancy-related deaths, with higher rates of mortality among women of color and women with lower incomes,” she said. “The rising trend in cardiovascular-related maternal deaths appears to be due to acquired, not congenital, heart disease.”

During her tenure as president of ACOG, Dr. Hollier convened a task force on cardiovascular disease in pregnancy that developed guidance that outlines screening, diagnosis, and management of CVD for women from prepregnancy through post partum.

Dr. Hollier noted that COVID-19 emphasizes racial disparities for maternal mortality.

“Pregnant patients with comorbidities, like heart conditions, may be at increased risk for severe illness from COVID-19 – consistent with the general population with similar comorbidities,” she said. “And as we know, black women’s risk of dying from CVD-related pregnancy complications is 3.4 times higher than that of white women. During the COVID-19 pandemic, we are seeing these racial health disparities exacerbated.”

However, any pregnant patients should not hesitate to communicate with their health care providers despite the pandemic situation, Dr. Hollier emphasized. “Communication between a patient and her ob.gyn., cardiologist, or other clinician is even more critical now during the COVID-19 pandemic. We’re hearing reports that patients who are experiencing symptoms or those with known cardiac conditions are avoiding the hospital and delaying or not seeking necessary treatment. This has the very real possibility of worsening the devastating maternal mortality crisis that we’re already experiencing in this country.”

To help overcome barriers to treatment, “collaboration between ob.gyns. and cardiologists, such as the cardio-obstetrics team or pregnancy heart team, is critical,” said Dr. Hollier. “These collaborative teams with a multidisciplinary approach can prospectively reduce the communication gaps across specialties when patients are seen separately. They can also improve the communication during care transitions such as between outpatient and inpatient care.


“In reviews of maternal deaths, we have found that there are often delays in diagnosis of heart conditions during and after pregnancy,” Dr. Hollier added. “Most maternal deaths from CVD are due to either undiagnosed cardiovascular disease or new-onset cardiomyopathy. ACOG recommends that all women be assessed for cardiovascular disease in the antepartum and postpartum periods using a recently developed algorithm,” she said. “Women who have known CVD and women who have concerning symptoms should have a consultation with this team. With increased awareness and screening, women can receive the additional care that they need.

“Because management of cardiac conditions in pregnancy is so complex, it is important to ensure that women receive care with teams and in facilities that have appropriate resources,” explained Dr. Hollier. “Women with known heart disease should see a cardiologist prior to pregnancy and receive prepregnancy counseling,” as noted in the AHA statement. “Patients determined to have moderate and high-risk CVD should be managed during pregnancy, delivery, and post partum in a medical center that is able to provide a higher level of care, including a cardio-obstetrics team.”

Early recognition of cardiovascular conditions is essential to help manage care and reduce risks to mother and baby, said Dr. Hollier. “Identification before a woman becomes pregnant means the patient’s care can be properly managed throughout the pregnancy and a detailed delivery plan can be developed through shared decision making between the patient and provider. We must think of heart disease as a possibility in every pregnant or postpartum patient we see to detect and treat at-risk mothers,” she said.

Additional research should focus on identifying risk factors prior to pregnancy, said Dr. Hollier. “There are often delays in recognizing symptoms during pregnancy and post partum, particularly for black women. We need data to understand which protocols are best to identify heart disease,”

Dr. Hollier had no financial conflicts to disclose. The authors of the AHA statement had no financial conflicts to disclose. The scientific statement was produced on behalf of the American Heart Association Council on Clinical Cardiology; Council on Atherosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

SOURCE: Mehta LS et al. Circulation. 2020 May 4. doi: 10.1161/CIR.0000000000000772.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

The meteoric rise in the number of test-positive and clinical cases of COVID-19 because of infection with the SARS coronavirus (SARS-CoV-2) in states and cities across the United States has added urgency to the efforts to develop protocols for hospital triage, admission, labor and delivery management, and other aspects of obstetrical care.

Emerging data suggest that, while SARS-CoV-2 is less lethal overall than the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) proved to be, it is significantly more contagious. Although a severe disease, the limited worldwide data so far available (as of early May) do not indicate that pregnant women are at greater risk of severe disease, compared with the general population. However, there remains a critical need for data on maternal and perinatal outcomes in women infected with SARS-CoV-2.

Multiple physiological changes in pregnancy, from reduced cell-based immune competence to changes in respiratory tract and pulmonary function – e.g., edema of the respiratory tract, increases in secretions and oxygen consumption, elevation of the diaphragm, and decrease in functional residual capacity – have historically contributed to worse obstetric outcomes in pregnant women who have had viral pneumonias. Furthermore, limited published experience with COVID-19 in China suggests worse perinatal outcomes in some affected pregnancies, including prematurity and perinatal death.

With evolution of the pandemic and accumulation of experience, it is expected that data-driven guidelines on assessment and management of infected pregnant women will contribute to improved maternal and perinatal outcomes. What is clear now, however, is that, without protecting the health of obstetricians and other health care workers, urgently needed gains in patient outcomes will not be realized.

Here are my recommendations, based on a currently limited body of literature on COVID-19 and other communicable viral respiratory disorders, as well my experience in the greater Detroit area, a COVID-19 hot spot.
 

Preparing for hospital evaluation and admission

The obstetric triage or labor and delivery (L&D) unit should be notified prior to the arrival of a patient suspected of or known to be infected with the virus. This will minimize staff exposure and allow sufficient time to prepare appropriate accommodations, equipment, and supplies for the patient’s care. Hospital infection control should be promptly notified by L&D of the expected arrival of such a patient. Placement ideally should be in a negative-pressure room, which allows outside air to flow into the room but prevents contaminated air from escaping. In the absence of a negative-pressure room, an infection isolation area should be utilized.

The patient and one accompanying support individual should wear either medical-grade masks brought from home or supplied upon entry to the hospital or homemade masks or bandanas. This will reduce the risk of viral transmission to hospital workers and other individuals encountered in the hospital prior to arriving in L&D. An ideal setup is to have separate entry areas, access corridors, and elevators for patients known or suspected to have COVID-19 infection. The patient and visitor should be expeditiously escorted to the prepared area for evaluation. Patients who are not known or suspected to be infected ideally should be tested.
 

Screening of patients & support individuals

Proper screening of patients and support individuals is critical to protecting both patients and staff in the L&D unit. This should include an expanded questionnaire that asks about disturbances of smell and taste and GI symptoms like loss of appetite – not only the more commonly queried symptoms of fever, shortness of breath, coughing, and exposure to someone who may have been ill.

Recent studies regarding presenting symptoms cast significant doubt, in fact, on the validity of patients with “asymptomatic COVID-19.” Over 15% of patients with confirmed infection in one published case series had solely GI symptoms and almost all had some digestive symptoms, for example, and almost 90% in another study had absent or reduced sense of smell and/or taste.^1,2 In fact, the use of the term “paucisymptomatic” rather than “asymptomatic” may be most appropriate.

Support individuals also should undergo temperature screening, ideally with laser noncontact thermometers on entry to the hospital or triage.
 

Visitor policy

The number of visitors/support individuals should be kept to a minimum to reduce transmission risk. The actual number will be determined by hospital or state policy, but up to one visitor in the labor room appears reasonable. Very strong individual justification should be required to exceed this threshold! The visitor should not only be screened for an expanded list of symptoms, but they also should be queried for underlying illnesses (e.g., diabetes, cardiovascular disease, significant lung disease, undergoing cancer therapy) as well as for age over 65 years, each of which increase the chances of severe COVID-19 disease should infection occur. The visitor should be informed of such risks and, especially when accompanying a patient with known or suspected COVID-19, provided the option of voluntarily revoking their visitor status. A visitor with known or suspected COVID-19 infection based on testing or screening should not be allowed into the L&D unit.

In addition, institutions may be considered to have obligations to the visitor/support person beyond screening. These include instructions in proper mask usage, hand washing, and limiting the touching of surfaces to lower infection risk.

“Visitor relays” where one visitor replaces another should be strongly discouraged. Visitors should similarly not be allowed to wander around the hospital (to use phones, for instance); transiting back and forth to obtain food and coffee should be kept to a strict minimum. For visitors accompanying COVID-19–-infected women, “visitor’s plates” provided by the hospital at reasonable cost is a much-preferred arrangement for obtaining meals during the course of the hospital stay. In addition, visitors should be sent out of the room during the performance of aerosolizing procedures.
 

Labor and delivery management

The successful management of patients with COVID-19 requires a rigorous infection control protocol informed by guidelines from national entities, such as the Centers for Disease Control and Prevention, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists, and by state health departments when available.

Strict limits on the number of obstetricians and other health care workers (HCWs) entering the patient’s room should be enforced and documented to minimize risk to the HCWs attending to patients who have a positive diagnosis or who are under investigation. Only in cases of demonstrable clinical benefit should repeat visits by the same or additional HCWs be permitted. Conventional and electronic tablets present an excellent opportunity for patient follow-up visits without room entry. In our institution, this has been successfully piloted in nonpregnant patients. Obstetricians and others caring for obstetrical patients – especially those who are infected or under investigation for infection – should always wear a properly fitted N95 mask.

Because patients with COVID-19 may have or go on to develop a constellation of organ abnormalities (e.g., cardiovascular, renal, pulmonary), it is vital that a standardized panel of baseline laboratory studies be developed for pregnant patients. This will minimize the need for repeated blood draws and other testing which may increase HCW exposure.

A negative screen based on nonreport of symptoms, lack of temperature elevation, and reported nonexposure to individuals with COVID-19 symptoms still has limitations in terms of disease detection. A recent report from a tertiary care hospital in New York City found that close to one-third of pregnant patients with confirmed COVID-19 admitted over a 2-week period had no viral symptoms or instructive history on initial admission.³ This is consistent with our clinical experience. Most importantly, therefore, routine quantitative reverse transcription polymerase chain reaction testing should be performed on all patients admitted to the L&D unit.

Given the reported variability in the accuracy of polymerase chain reaction testing induced by variable effectiveness of sampling techniques, stage of infection, and inherent test accuracy issues, symptomatic patients with a negative test should first obtain clearance from infectious disease specialists before isolation precautions are discontinued. Repeat testing in 24 hours, including testing of multiple sites, may subsequently yield a positive result in persistently symptomatic patients.
 

Intrapartum management

As much as possible, standard obstetric indications should guide the timing and route of delivery. In the case of a COVID-19–positive patient or a patient under investigation, nonobstetric factors may bear heavily on decision making, and management flexibility is of great value. For example, in cases of severe or critical disease status, evidence suggests that early delivery regardless of gestational age can improve maternal oxygenation; this supports the liberal use of C-sections in these circumstances. In addition, shortening labor length as well as duration of hospitalization may be expected to reduce the risk of transmission to HCWs, other staff, and other patients.

High rates of cesarean delivery unsurprisingly have been reported thus far: One review of 108 case reports and series of test-positive COVID-19 pregnancies found a 92% C-section rate, and another review and meta-analysis of studies of SARS, MERS, and COVID-19 during pregnancy similarly found that the majority of patients – 84% across all coronavirus infections and 91% in COVID-19 pregnancies – were delivered by C-section.4,5 Given these high rates of cesarean deliveries, the early placement of neuraxial anesthesia while the patient is stable appears to be prudent and obviates the need for intubation, the latter of which is associated with increased aerosol generation and increased virus transmission risk.

Strict protocols for the optimal protection of staff should be observed, including proper personal protective equipment (PPE) protection. Protocols have been detailed in various guidelines and publications; they include the wearing of shoe covers, gowns, N95 masks, goggles, face shields, and two layers of gloves.

For institutions that currently do not offer routine COVID-19 testing to pregnant patients – especially those in areas of outbreaks – N95 masks and eye protection should still be provided to all HCWs involved in the intrapartum management of untested asymptomatic patients, particularly those in the active phase of labor. This protection is justified given the limitations of symptom- and history-based screening and the not-uncommon experience of the patient with a negative screen who subsequently develops the clinical syndrome.

Obstetric management of labor requires close patient contact that potentially elevates the risk of contamination and infection. During the active stage of labor, patient shouting, rapid mouth breathing, and other behaviors inherent to labor all increase the risk of aerosolization of oronasal secretions. In addition, nasal-prong oxygen administration is believed to independently increase the risk of aerosolization of secretions. The casual practice of nasal oxygen application should thus be discontinued and, where felt to be absolutely necessary, a mask should be worn on top of the prongs.

Regarding operative delivery, each participating obstetric surgeon should observe guidelines and recommendations of governing national organizations and professional groups – including the American College of Surgeons – regarding the safe conduct of operations on patients with COVID-19. Written guidelines should be tailored as needed to the performance of C-sections and readily available in L&D. Drills and simulations are generally valuable, and expertise and support should always be available in the labor room to assist with donning and doffing of PPE.
 

Postpartum care

Expeditious separation of the COVID-19–positive mother from her infant is recommended, including avoidance of delayed cord clamping because of insufficient evidence of benefit to the infant. Insufficient evidence exists to support vertical transmission, but the possibility of maternal-infant transmission is clinically accepted based on small case reports of infection in a neonate at 30 hours of life and in infants of mothers with suspected or confirmed COVID-19.6,7 Accordingly, it is recommended that the benefit of early infant separation should be discussed with the mother. If approved, the infant should be kept in a separate isolation area and observed.

There is no evidence of breast milk transmission of the virus. For those electing to breastfeed, the patient should be provided with a breast pump to express and store the milk for subsequent bottle feeding. For mothers who elect to room in with the infant, a separation distance of 6 feet is recommended with an intervening barrier curtain. For COVID-19–positive mothers who elect breastfeeding, meticulous hand and face washing, continuous wearing of a mask, and cleansing of the breast prior to feeding needs to be maintained.

Restrictive visiting policies of no more than one visitor should be maintained. For severely or critically ill patients with COVID-19, it has been suggested that no visitors be allowed. As with other hospitalizations of COVID-19 patients, the HCW contact should be kept at a justifiable minimum to reduce the risk of transmission.